Oral co-delivery nanoemulsion of 5-fluorouracil and curcumin for synergistic effects against liver cancer

ABSTRACT

Background

A novel nanoemulsion (CU/FU-LN) was developed as an oral 5-fluorouracil and curcumin co-delivery system for synergistic efficacy against liver cancer.

Methods

MTT assay, confocal laser scanning microscope, and H&E staining were utilized to establish the efficacy and safety of CU/FU-LN.

Results

The AUC_(0-t) of CU/FU-LN was 8.85-fold and 8.59-fold greater than those of CU and FU, respectively. The IC₅₀ of CU/FU-LN was 4.6-fold and 4.9-fold lower than those of FU and CU in HepG2 cells, respectively. In vivo anti-tumor trials, the tumor inhibition rate was significantly elevated by CU/FU-LN (49.29%), compared 24.84% and 4.72% for FU and CU, respectively. Ki-67 immunohistochemical analysis revealed that CU/FU-LN had an obvious anti-proliferation effect. The IC₅₀ of CU/FU-LN in L02 cells was 1.51-fold and 2.60-fold higher than those of CU and FU, respectively. Certain vital organs in the mice of the CU/FU-LN group showed markedly fewer lesions than those of the CU, FU, and CU+FU groups. The CU/FU-LN treatment caused no significant change in mouse body weight relative to the control group (P > 0.05). 

Conclusions

We successfully prepared a promising co-delivery platform for the synergistic treatment of liver cancer and it has a comparatively enhanced efficacy and mitigated toxicity.

KEYWORDS:

• Co-delivery
• curcumin
• 5-fluorouracil
• liver cancer
• oral nanoemulsion
• synergy

Author contributions

P Guo, C Pi,and S Zhao were involved in performing experiments and writing the manuscript. S Fu, H Yang, X Zheng, and X Zhang were involved in analysis and interpretation of the data. L Zhao and Y Wei were involved in conception, design, and revising the paper.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Expert opinion

At present, oral administration remains the primary and convenient means of treatment against liver cancer. A novel oral co-deivery nanoemulsion (CU/FU-LN) loaded with curcumin and 5-fluorouracil was prepared with synergistic effects including elevation of efficacy and safety in the treatment of liver cancer, based on results with cellular and animal models. Therefore, CU/FU-LN would be a promising method against liver cancer.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from Expert Opinion on Drug Delivery for their review work, but have no other relevant financial relationships to disclose.

Additional information

Funding

This study was supported by the basic research fund of the science and technology department of Sichuan province of China (No. 2020YJ0336, 2020YJ0373), the Joint Fund of Luzhou City and Southwest Medical University (No. 2017LZXNYD-T02, 2019LZXNYDZ07), the Science and Technology Fund of Luzhou science and technology and Human Resources Bureau (No. 2019-SYF-35), Science and Technology Innovation Team from Jiucheng Science and Technology Talent Cultivation Plan in Luzhou City (2019-1).